mmg_233_2013_genetics_genomicswikiaorg-20200214-history
Structural Genomics Consortium
Structural Genomics Consortium The Structural Genomics Consortium (SGC) is a not for profit public-private consortium based out of the Universities of Oxford and Toronto. It was started in 2004 with its primary goal being the discovery of potential drug targets and making this information freely available to the public. The SGC is currently responsible for the determination of greater than 25% and 50% of all human and human parasite protein structures, respectively, deposited in the Protein Data Bank (PDB) each year. In order to discover new drug targets, human proteins of biomedical importance as well as the proteins of human parasites are identified. The ability to determine what proteins may be important is greatly enhanced by the availability of the human genome as well as any genetic information available on human parasites. After identification, the three dimensional structure of the target protein is determined. Structure determination will then allow for better drug design. Once the structure is determined it is published on the SGC website (thesgc.org) as well as being submitted to the PDB. In addition to the structure, other relevant information is published as well. This includes the information needed to express the protein such as the expression vector used, the expression host (i.e. E.Coli),gene ascension number, the construct sequence including weather the protein was tagged (i.e. his tag) or mutated. Information on protein purification is also published including how it was purified what buffers were used during purification. Furthermore background information of the protein is also included as well as its PDB identification number if it has been published there as well. The structural information provided by the SGC has furthered the study of several fields including signal transduction, specifically how tyrosine kinases function2, how the histone modifying protein JMJD2A recognizes substrates3, and how cytosolic sulfotransfases are involved in drug and hormone metabolism4. How to Use the Database In order to use SGC, first the name of a protein of interest is entered into the search bar (Figure 1). For this example Glutathione Peroxidase 1 is used. Following the search, the results will be displayed (Figure 2). In order to see the protein information the structures tab must be selected. Next select the protein of interest's name (Figure 3). By selecting the name you gain access to the three dimensional structure as well as additionally tabs (Figure 4) that you can select. By selecting the materials and methods tab information on how protein was expressed and purified (Figure 5) can be accessed. By selecting the slideshow tab (Figure 6) a more detailed discussion of how the structure of the protein relates to its function can be accessed. '' '''Sources ' 1. www.thesgc.org 2. Filippakopoulos P., Kofler M., Hantschel O., Gish GD., Grebien F., Salah E., Neudecker P., Kay LE., Turk BE., Superti-Furga G., Pawson T., Knapp S. (2008). Structural coupling of SH2-kinase domains links Fes and Abl substrate recognition and kinase activation. Cell, 134(5), 793-803. 3. Ng SS., Kavanagh KL., McDonough MA., Butler D., Pilka ES., Lienard BM., Bray JE., Savitsky P., Gileadi O., von Delft NR., Offer J., Scheinost JC., Borowski T., Sunderstrom M., Schofield CJ., Opperman U. (2007). Crystal structures of histone demethylase JMJD2A reveal basis for substrate specificity. Nature, 448(7149), 87-91. 4. Allali-Hassani A., Pan PW., Dombroski L., Najmanovich R., Tempel W., Dong A., Loppnau P., Martin F., Thornton J., Edwards AM., Bocharev A., Plotnikov AN., Vedadi M., Arrowsmith CH. (2007). Structural and chemical profiling of the human cytosolic sulfotransferases. PLoS Biology, 5(5), 1063-1078.